Expression and Prognostic Characteristics of m6 A RNA Methylation Regulators in Breast Cancer

Zhang, Bo; Gu, Yanlin; Jiang, Guoqin

doi:10.3389/fgene.2020.604597

Cited by 54 publications

(55 citation statements)

References 43 publications

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“…Thus, METTL16 is considered a protective gene, suppressing the development of OC, HCC, and endocrine system tumors [ 98 , 99 , 100 ]. However, the high expression of METTL16 has been linked with poor survival rate in patients with breast cancer [ 101 ]. Finally, METTL16 is known to specifically recognize oncogenic lncRNA, MALAT1.…”

Section: Mettl16 In Cancermentioning

confidence: 99%

METTL16, Methyltransferase-Like Protein 16: Current Insights into Structure and Function

Ruszkowska

2021

IJMS

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Methyltransferase-like protein 16 (METTL16) is a human RNA methyltransferase that installs m6A marks on U6 small nuclear RNA (U6 snRNA) and S-adenosylmethionine (SAM) synthetase pre-mRNA. METTL16 also controls a significant portion of m6A epitranscriptome by regulating SAM homeostasis. Multiple molecular structures of the N-terminal methyltransferase domain of METTL16, including apo forms and complexes with S-adenosylhomocysteine (SAH) or RNA, provided the structural basis of METTL16 interaction with the coenzyme and substrates, as well as indicated autoinhibitory mechanism of the enzyme activity regulation. Very recent structural and functional studies of vertebrate-conserved regions (VCRs) indicated their crucial role in the interaction with U6 snRNA. METTL16 remains an object of intense studies, as it has been associated with numerous RNA classes, including mRNA, non-coding RNA, long non-coding RNA (lncRNA), and rRNA. Moreover, the interaction between METTL16 and oncogenic lncRNA MALAT1 indicates the existence of METTL16 features specifically recognizing RNA triple helices. Overall, the number of known human m6A methyltransferases has grown from one to five during the last five years. METTL16, CAPAM, and two rRNA methyltransferases, METTL5/TRMT112 and ZCCHC4, have joined the well-known METTL3/METTL14. This work summarizes current knowledge about METTL16 in the landscape of human m6A RNA methyltransferases.

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Section: Mettl16 In Cancermentioning

confidence: 99%

METTL16, Methyltransferase-Like Protein 16: Current Insights into Structure and Function

Ruszkowska

2021

IJMS

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“…In addition, the log-rank survival analysis suggested that the RC patients with lower expression of these two genes have a remarkable worse overall survival with P < 0.05 ( Figures 1E,F ). Additional m 6 A regulators, including HNRNPA2B1, RBM15B, RBMX, METTL16, FMR1, and LRPPRC, reported in a recent study ( Zhang et al, 2020 ), were also analyzed ( Supplementary Figure 2 ). The log-rank survival analysis suggested that the RC patients with lower expression of RBMX and LRPPRC have a remarkable worse overall survival with P = 0.012 and P = 0.003, respectively.…”

Section: Resultsmentioning

confidence: 99%

Prognostic Implication of the m6A RNA Methylation Regulators in Rectal Cancer

et al. 2021

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N6-methyladenosine (m6A) is a very common and abundant RNA modifications occurring in nearly all types of RNAs. Although the dysregulated expression of m6A regulators is implicated in cancer progression, our understanding of the prognostic value of the m6A regulators in rectal cancer is still quite limited. In this study, we analyzed the RNA expression levels of the 17 m6A regulator genes of 95 rectal cancer and 10 normal rectal samples from the The Cancer Genome Atlas Rectum Adenocarcinoma (TCGA-READ) dataset. Lasso regression analysis was conducted to build a prognostic model and calculate the risk score. The rectal cancer patients were then devided into the high-risk and low-risk groups according to the mean risk score. The prognostic value of the identified model was separately evaluated in the TCGA-READ and GSE87211 datasets. GSEA was conducted to analyze the functional difference of high-risk and low-risk rectal cancer patients. Our analysis revealed that rectal cancer patients with lower expression of YTHDC2 and METTL14 had a remarkable worse overall survival (P < 0.05). The prognostic value of the model was validated in GSE87211 datasets, with AUC = 0.612 for OS and AUC = 0.651 for RFS. Furthermore, the m6A modification-based risk score system is associated with activation of distinct signaling pathways, such as DNA repair, epithelial-mesenchymal transition, G2M checkpoint and the MYC pathway, that may contribute to the progression of rectal cancer. In conclusion, our findings demonstrated that the m6A RNA methylation regulators, specifically YTHDC2 and METTL14, were significantly down-regulated and might be potential prognostic biomarkers in rectal cancer.

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“…It has been demonstrated that FTO can regulate cell migration and invasion in breast cancer via the miR-181b-3p/ARL5B signaling pathway, and high FTO expression is associated with advanced breast cancer staging [ 32 ]. A recent study also showed that tumor status and stage were relevant to the expression level of m 6 A RNA methylation regulators [ 33 ]. The m 6 A in peripheral blood RNA is closely associated with breast cancer stage [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

N6-Methyladenosine Regulators Are Involved in the Progression of and Have Clinical Impact on Breast Cancer

et al. 2021

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Background N6-methyladenosine (m 6 A) modification has been widely studied in various cancers, and m 6 A regulators, such as METTL3, METTL14, WTAP, and YTHDF1, play crucial roles in breast cancer. However, a comprehensive study of m 6 A regulators in breast cancer is still lacking. Material/Methods Expression data of m 6 A regulators and clinicopathological information were acquired from The Cancer Genome Atlas (TCGA) program. Protein interaction was collected from the STRING database. Data on tumor purity and correlation among m 6 A regulators were obtained from the TIMER database. LASSO, consensus clustering, and gene set enrichment analysis (GSEA) were used to evaluate the role of m 6 A regulators. Moreover, the prognostic value of m 6 A-related genomic targets in breast cancer was analyzed by Kaplan-Meier analysis and Cox regression models. Results We found most m 6 A regulators were associated with key clinicopathological parameters, such as tumor staging, Nottingham prognostic index (NPI), and cellularity. Also, consensus clustering analysis-based grouping could effectively predict patients’ overall survival. Correlation analysis also showed that these regulators interacted with each other. Patients were further split into a high-risk group and low-risk group based on Cox and LASSO analysis. High-risk patients had a significantly worse overall survival than did low-risk patients. Moreover, AKT1 and MYC were enriched in patients in the high-risk group, according to GSEA analysis. The patients in the high-risk group also displayed resistance to chemoradiotherapy or hormone therapy. Conclusions The m 6 A regulators are critical participants in the development and progression of breast cancer and are likely to be used to predict prognosis and develop treatment strategies.

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Expression and Prognostic Characteristics of m6 A RNA Methylation Regulators in Breast Cancer

Cited by 54 publications

References 43 publications

METTL16, Methyltransferase-Like Protein 16: Current Insights into Structure and Function

METTL16, Methyltransferase-Like Protein 16: Current Insights into Structure and Function

Prognostic Implication of the m6A RNA Methylation Regulators in Rectal Cancer

N6-Methyladenosine Regulators Are Involved in the Progression of and Have Clinical Impact on Breast Cancer

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